JPS61218590A - Production of 2,6-bis(4-hydroxy-3,5-dimethoxyphenyl)-3,7-dioxabicyclo (3.3.0)octane - Google Patents

Abstract

PURPOSE:Plant bodies containing lignin with syringly nuclei are heated under moist conditions in a pressure vessel, the injected out under normal pressure, then the treated product is extracted with an organic solvent to obtain the titled compound of high purity, which is used as a tonic in high yield. CONSTITUTION:Plants containing lignins bearing syringly nuclei such as broad leaf trees or bamboos are placed in a tightly sealable vessel and heated, preferably introducing saturated steam at 10-40kg/cm<2> into the vessel to effect treatment with moist heat. Then, the product is jetted out into the receiver under normal pressure and extracted with an organic solvent such as tetrahydrofuran, further the extract is dissolved in ether or the like, and the soluble fraction is purified in a know manner to obtain the objective compound. In order to effect rapid jetting of the plant-treating product, the use of highly air-tight equipment such as ball valves as switching valves is recommended.

Description

Detailed Description of the Invention (Industrial Field of Application) 2,6-bis(4-hydroxy-3,5-dimethoxyphenyl)-3,7-thioxabicyclo[3,3,01 octane, i.e. syringe The present invention relates to a method for producing cinol and its stereoisomers (hereinafter abbreviated as syringaresinols) at a high yield and at low cost.

(Prior art) Syringaresinol, which is classified as a lignan, which is a type of plant component, exists in hardwoods and herbs together with its glycosides, although in small amounts. It is known that it is contained in lignin, which is one of the major chemical components of this class. On the other hand, recently in our country, Eleuthero (Acanth).

-panax 5 enticosus) is attracting attention as being effective in strengthening and enhancing biological defenses, similar to ginseng, which is widely used as a medicinal plant. The existence of bodies has been reported primarily by Soviet scientists. However, although syringaresinol has been attracting attention as a new physiologically active substance, no efficient and economical method has been considered for its production, and only a few methods have been developed using plant ingredient chemistry. Only laboratory separation methods have been reported in the research field.

As mentioned above, syringaresinol exists as a glycoside in the extracted components of hardwood wood, and can be extracted along with many other components by directly immersing the wood and stalk in water-containing methanol. Ru. In this case, the amount of syringaresinol extracted is generally extremely small, less than 0.01% of the total material, and is considered to have a relatively high content. (Liri
Even if the endothelial content of Dendrontulipifera is about 0.85%, a complicated separation process is required, and the resulting syringaresinol must also be extremely expensive.

Furthermore, in this method of directly extracting resin from the material, six types of resinols with very similar structures coexist. That is, in the following formula (1), R+, ==R2=R, 3=+=
In addition to syringaresinol consisting of a syringyl nucleus when R,,==OCH3, R1=R3=OCH3゜几2=
1. Virginol consisting of a guaiacyl nucleus in the case of =R, =H and R1=R2=R3=OCR3. Furthermore, since medioresinol consisting of both guaiacyl and syringyl branches when R4=H is present, a more advanced separation treatment is required to isolate pure syringaresinol.

Among herbs, Artimjsiaabs
inthum), periwinkle (Vincama
jOr ) + = Vinca rose
Syringaresinol has been found in extract components such as a), but both are in very small amounts.

On the other hand, woody plants and herbaceous plants have 20 to 60 chi and 15 to 60 chi, respectively.
Contains 25% lignin. Lignin is produced by hydroxycinnamyl alcohols, which are monolig tools (primary structural units), being dehydrogenated by enzymes in plants, forming phenoxy radicals, and the resonance body of which undergoes radical polymerization. It has been revealed that dilignol (secondary structural unit) is produced, and this dilignol is further polymerized to become a polymer in sequence, and finally becomes a polymer substance with a complex three-dimensional network structure. Typical bond types of dilignol include allylglycerol-α and allylglycerol-α-
The presence of allyl ether, phenyl coumaran, biphenyl, and diallyl propane) and resinols have also been confirmed, but their amounts are small compared to the former four. Since the composition ratio of parahydroxycinnamyl alcohol, which is a siliconolignol, differs depending on the type of plant, the type and amount ratio of the siliconol produced also differ. In the following formula (Wataru), coniferous lignin is almost entirely R,==OC)
t3. When R2=)l; 7 erylal"-1'
Broad leaf m/Ninha, coniferyl alcohol and R1=
When 几2=oct-i3, cinavir alcohol is 1:
1. Herbaceous lignin has both R,=R2=H
The ratio of alcohol in the case of alcohol is approximately 4.5:4
, 5:1, and syringaresinol is incorporated into macromolecules of broad-leaved and herbaceous lignins containing syringyl units through ether bonds.

H Conventionally, as a method for obtaining syringaresinol from these lignins, syringaresinol using hot water [Chem,
Bet, vol, 9B, p 538 (196
5) ] Dioxane steaming [Journal of the Japan Society of Wood Science; vo
1, 17, p464 (1971)], or high-pressure hydrogenolysis using a metal catalyst such as copper-chromium oxide [Journal of the Japan Society of Wood Science; Vol. 19. p1
65 (1973)), but all of these methods are separation methods in the field of research on the chemical structure of lignin and have little meaning as industrial production methods.

Furthermore, there is also a laboratory synthesis method for syringaresinol.
However, in all of these cases, it is not easy to obtain large amounts of starting materials with a syringyl nucleus, and the synthesis steps from the starting materials to the final syringaresinol are complex and varied, making them meaningless as industrial production methods. It can be said that there is no such thing.

(Problems to be Solved by the Invention) The present invention aims to provide a method for producing syringaresinols on an industrial scale in place of conventional production methods such as constriction.

(Means for Solving the Problems) From the viewpoint of effective utilization of wood resources, the present inventors have found that it is easy to separate the components of wood, and there is a high possibility of using all the obtained components. In the process of investigating how wood components change through blasting treatment, which is attracting attention as a pre-treatment for wood resources, that is, treatment with high-temperature, high-pressure steam followed by exposure to a rapid depressurization state. It has been found that syringaresinol can be obtained in surprisingly good yields by blasting broad-leaved trees and herbs.

The present inventors have already participated in a symposium [Biomass and Biotechnology%'83 (1985)].

[Wood Research (Kyoto University); Bian 69. p56-51 (198
5)), C polymer processing; Vol, 52, A12, p5
9-47 (1983)], it was recognized that the wood structure was easily destroyed and defibrated by holding water-containing wood chips at high temperature and high pressure and then rapidly reducing the pressure, and it was found that the wood structure was easily destroyed and defibrated, and new pulp was developed. Although this method was shown to be interesting as a chemical reaction method, it was also observed that lignin was cleaved and decomposed into low-molecular compounds that were soluble in organic solvents. Using hardwood chips, they were held under various conditions of high temperature and high pressure, and then the pressure was rapidly reduced.The treated product was extracted with an organic solvent, and the soluble portion was examined, and it was found that syringaresinol The present invention has been completed because it is clear that a large amount of the above-mentioned substances are contained.

The present invention involves sealing a plant, such as a hardwood chip, containing syringyl core and rigenin as a component in a pressure vessel, pressurizing and heating it in a water-containing state, and then rapidly discharging it into a receiving tank under normal pressure. According to the present invention, a novel method for producing syringaresinol is provided, in which the wood chips are pulverized into fine particles, and then extracted and purified using an organic solvent such as methanol. Syringaresinols can be economically obtained in good yield from readily available raw materials.

The process for producing syringaresinol of the present invention involves pressurizing and heating a hydrous plant body with saturated steam, instantly discharging it under atmospheric pressure, and extracting the finely powdered plant body with an organic solvent. These steps will be explained in detail below.

The raw material plant used in the present invention is a broad-leaved tree.

Any material that contains lignin containing syringyl kernels, such as bamboo, straw, cottonseed husks, coconut husks, and almond husks, can be used, but if the content is low, there will be a lot of impurities, and the purification process will be complicated. Since this is economically disadvantageous, it is preferable that the Klason ligoon contains 5% or more of the plant body.

In order to ensure uniformity of the reaction and homogenization of destruction, it is preferable that the raw material subjected to the pressurized O heat treatment be made into a water-containing body with a water content of 10 g or more. Occasionally, a uniform moisture content is obtained by coagulating drainage. Therefore, the raw material need not be extremely overdried.

In addition, in consideration of workability and destruction efficiency, the shape of the raw material should preferably be chips or small pieces of no more than a few.

The above water-containing plant body is placed in a jacketed pressure vessel, and at the same time, the air inside the vessel is replaced with low pressure steam of about 1 to 2 kg/-. Subsequently, the entire container including its contents is heated, and at the same time, saturated steam is blown in to a predetermined pressure.

The treatment pressure is 10 to 40 kg/-, and if it is less than 10 kg/15 i, the softening of the plant tissue, that is, the solubilization of hemicellulose by hydrolysis and the low molecular weight reaction of lignin, are insufficient, and the The amount produced will also be small. In addition, the higher the pressure and heating, the faster the reaction progresses, and the yield of syringaresinol tends to be higher, but at 25 kg/-
The yield rate is the slowest at the highest temperature, and even at higher temperatures and pressures, the processing time is shortened, but the yield does not increase.

On the other hand, extreme pressurization and heating exceeding 40 kg/- is disadvantageous because there is a risk of partial carbonization, requires care, and requires expensive equipment.

The temperature and pressure holding time to obtain the highest yield varies depending on the stb of the raw material plant, but a short time of at most 20 minutes is sufficient for 25 kg/-, and 10 minutes or less for 50 kg/-.

Next, the pressurized and heated water-containing plant body is discharged through a thin tube into a receiving tank under normal pressure equipped with a muffling tube in an extremely short period of time. In order to perform instantaneous discharge, it is appropriate to use a device with excellent airtightness such as ball pulp or rotary pulp as an on-off valve.

The rapid vaporization of high-temperature, high-pressure water that occurs during discharge, and the mechanical shock or friction between the plants and between the plants and the tube wall that occurs when the heated and pressurized water-containing plants pass through the tubules. By this process, a homogeneously finely ground plant body is obtained, and the hemicellulose in the fine powdered water-containing plant body is hydrolyzed and becomes soluble in water, and the lignin is reduced to a low molecular weight and becomes oil droplets that are released outside the cells. Since it is in the discharged state, the lignin decomposition products containing syringaresinols are very easily extracted by organic solvents.

The finely powdered hydrated plant body obtained in this way is suspended in a water-miscible solvent such as methanol, ethanol, dioxane, tetrahydrofuran, etc. as it is or in advance in several times the amount of water. After filtering to remove the water-soluble part of the sugar fat, it is soaked to extract syringaresinol along with the lignin decomposition product. The residue obtained by distilling off the solvent from the extract is a dark brown solid. This product may be purified by a known method, but since it contains many impurities and its purity is low, it is further dissolved in ether, ester, aromatic hydrocarbon, or chlorinated hydrocarbon, and the soluble portion is collected. It is more efficient to purify the target product with high purity.

In addition, the water-containing fine powder is freeze-dried or dried under reduced pressure to remove water and produce ethers and esters.

It may also be extracted with aromatic hydrocarbons or chlorine-substituted hydrocarbons. When the solvent is distilled off from the extract, a solid substance containing 5 to 15 units of lingaresinol is obtained. The yield of this solid material varies depending on the type of raw material plant, but in the case of broad-leaved trees, it reaches 10 to 15 units per dry weight.

Highly pure syringaresinol can be obtained by purifying the obtained solid substance according to known methods such as recrystallization or various types of atomography.

The syringaresinol obtained in the present invention is a mixture of syringaresinol and evisyringaresinol, and is optically a d,7-form.

(Function) According to the present invention, syringaresinol can be obtained in a much larger amount than the amount originally present in the lignin and extracted components of the raw material plant. The detailed mechanism of its formation will have to wait for future research including model experiments, but it can be thought of as follows.

Lignin in plants is produced through the catalytic action of activated water at high temperature and high pressure and acetic acid generated by hydrolysis of acetyl groups in hemicellulose, and the most important bonds in lignin are allylglycerol-α and lignin. The β-allyl ether is cleaved and sequentially reduced in molecular weight, and one molecule of water is removed from the syringylglycerol-β-allyl ether bonding portion represented by the following formula (i), resulting in the following (
A quinone methide structure of formula N) is formed, and then the β-allyl ether bond is radically cleaved to produce a quinone methide radical of the following formula (v). After the two molecules of the ginone methide radical are recoupled, a ring is formed to produce syringaresinol.

The produced syringaresinol has a stable side chain structure, and the aromatic ring is stable because it is based on the ortho and para positions of the phenolic hydroxyl group, and the only reactive position is the phenolic hydroxyl group, producing phenyl ether. Even if it does, it is thought that the trap will disintegrate immediately and return to the original syringaresinol.

(~ As reported by the present inventors in the 66th Japan Wood Society Conference Research Presentation Abstracts; p. 283 (1985), lignin decomposition products obtained by blasting hardwood materials under strong conditions contain It was confirmed by nuclear magnetic resonance spectroscopy that the allylglycerol-β-allyl ether bond had almost disappeared.

In addition, in in vitro enzymatic dehydrogenation polymerization or dehydrogenation polymerization using an oxidizing agent, which is a typical radical reaction of cinnavir alcohol, syringaresinol is usually converted to 70 to 90 molecules via a quinone methide radical. It has also been revealed that the product is produced with a yield of [Wond
Re5earch ;461゜p44 Sat56(1
976)].

Therefore, under the conditions of the present invention, the quinone methide radical of formula (V) is generated due to the cleavage of the syringyl glycerol-β-allyl ether bond in the lignin containing the syringyl nucleus, and the quinone methide radical once generated is It is believed that tradecal recondenses, resulting in the production of a large amount of syringaresinol. Also, according to these conditions, pressurization/
Since the entire reaction system becomes acidic during the heat treatment, syringaresinol is in a state where it easily changes to shrimpyringaresinol. Therefore, it is considered that the evisyringaresinol obtained in the present invention is produced by changing the syringaresinol produced by the mechanism described above.

(Effects of the Invention) According to the present invention, syringaresinols can be produced at extremely high yields using readily available and inexpensive plants such as hardwood, bamboo, and coconut shells as raw materials. Moreover, neither the process of pulverizing the plant body nor the extraction process using an organic solvent requires complicated manufacturing equipment or processing operations.
It is easy to industrialize, and high profits can be expected.

(Example) Hereinafter, the present invention will be specifically explained based on Examples.

[Example 1] A pressure vessel (withstand pressure 40 kg/-, capacity 21), which has a steam blowing pipe and an air discharge pipe in the upper part, a discharge pipe with a ball valve in the lower part, and a receiver tank with a silencer, is made of beech wood. The chip was sealed in a dry weight of 200 g. Next, open the air exhaust pipe and pump 2kg15 for 2-3 seconds at a time! Blow in saturated steam from the gauge and expel the air, repeat this operation 3 times.
It was repeated several times. After steam replacement, close the air exhaust pipe and
Kg/-gauge saturated steam was introduced into the pressure vessel and jacket and rapidly heated and pressurized. The maximum temperature reached in the container was 235°C. Immediately after reaching 235°C, the introduction of saturated steam was stopped, and this state was maintained for 8 minutes.

Thereafter, the lower ball valve was opened, and the contents of the pressure vessel were discharged into the receiving tank within a very short time. The ejection time is almost instantaneous. The inside of the receiving tank was washed with water, and the fine beech powder discharged was collected as a suspension.

Add water to the obtained fine powder suspension to make the total amount 31,
After stirring, the mixture was filtered under suction. Furthermore, the same operation was repeated twice. The filtration residue was dispersed in 21 methanol, stirred, and filtered. Repeat the same process two more times, totaling 6
The two methanol solutions were combined and concentrated to dryness.

The amount of methanol extract obtained was 52 g.

This methanol extract was dissolved in 200ml of dioxane, and added dropwise to ethyl ether No. 21 with stirring, the precipitate was filtered off, and the ether-soluble portion was collected. Distilling off the ether gave 30 g of solid residue.

This solid was charged to a column packed with silica gel C-200 manufactured by Wako Co., Ltd., and methanol:chloroform/1
:99 (volume ratio), and a portion containing syringaresinol was collected while monitoring by silica gel thin layer chromatography. When the solvent was distilled off from the collected eluate, crude crystals containing syringaresinol 6 were obtained.
g was obtained.

When this crude crystal was recrystallized from ethanol-chloroform, 2.5 g of crystals consisting only of syringaresinol and evisyringaresinol were obtained, and high-performance liquid chromatography gave peaks that matched those of each sample. .

[Example 2] Moso bamboo strips with a dry weight of 200 g were prepared in Example 1.
Heat and pressure treatment was performed in the same manner as in Example 1 using saturated steam of 28 kg/i gauge, maximum temperature of about 250 ° C., and maximum temperature holding time of 10 minutes. and then exhaled.

The obtained fine powder suspension was subjected to water and methanol extraction treatment in the same manner as in Example 1 to obtain 47 g of dry methanol extract.
I got it. 200 μml of this methanol extract was also dissolved in an ethanol/2:1 (volume ratio) solution, and added dropwise to ethyl ether in the same manner as in Example 1.
22 g of ether soluble portion was obtained.

This ether-soluble part was treated with silica gel C-200 manufactured by Wako Co., Ltd.
was charged to a column packed with 2:3 and eluted with a mixture of benzene:ethyl acetate/2:1 (volume ratio), and subjected to silica gel thin layer chromatography. Subsequently, the syringaresinol portion was collected. When the solvent was distilled off from the collected eluate, 1.7 g and 1.6 g of crude crystals of Ebishiri/Garesinol and Syringaresinol were obtained, respectively.

When each crude crystal was recrystallized from methanol-chloroform, 1.5 g and 0.9 g of pure crystals of Ebishiri/Garesinol and Syringaresinol were obtained, respectively, and the melting point and N
The M spectrum was consistent with that in the literature.

[Example 5] Cotton seed husks with a dry weight of 200 g were used in a saturated steam bath of 2
5 kg/- gauge, maximum temperature approximately 220 tl:.

The apparatus of Example 1 under the conditions of maximum temperature holding time of 12 minutes.

A fine powder suspension was obtained by processing according to the procedure.

The obtained fine powder suspension was subjected to water and methanol extraction treatment in the same manner as in Example 1 to obtain 94 g of dry methanol extract.
I got it. This methanol extract was treated under the same conditions and procedure 2 as in Example 1 to obtain 1.8 g of crystals consisting only of syringaresinol and evisyringaresinol.

Claims (6)

[Claims] (1) A plant body containing lignin containing syringyl kernels as a component is sealed in a pressure vessel, pressurized and heat-treated in a water-containing state, and then rapidly discharged into a receiving tank under normal pressure.
2,6-bis(4-hydroxy-3,5-dimethoxyphenyl)-3,7-dioxabicyclo[3,3,0], which is characterized in that the processed product of the plant is extracted with an organic solvent.
How to make octane. (2) Items 2 and 6 of Claim 1, characterized in that the plant is a woody broad-leaved tree or a herbaceous plant.
A method for producing -bis(4-hydroxy-3,5-dimethoxyphenyl)-3,7-dioxabicyclo[3,3,0]octane. (3) 2 as set forth in claim 2, characterized in that the pericarp of a broad-leaved tree or the seed coat of a herb is used as the plant body.
, 6-bis(4-hydroxy-3,5-dimethoxyphenyl)-3,7-dioxabicyclo[3,3,0]octane. (4) The second aspect of claim 1, characterized in that alcohols, ethers, esters, chlorine-substituted hydrocarbons, or aromatic hydrocarbons are used as the organic solvent.
, 6-bis(4-hydroxy-3,5-dimethoxyphenyl)-3,7-dioxabicyclo[3,3,0]octane. (5) 2,6-bis(4-hydroxy-3,5-dimethoxyphenyl)- according to claim 1, characterized in that saturated steam is used during the pressurization and heat treatment.
A method for producing 3,7-dioxabicyclo[3,3,0]octane. (6) 2,6- as set forth in claim 5, characterized in that saturated steam of 10 to 40 kg/cm^2 is used.
Bis(4-hydroxy-3,5-dimethoxyphenyl)
- A method for producing 3,7-dioxabicyclo[3,3,0]octane.